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PubMed1972

Transduction of tetracycline resistance in Staphylococcus epidermidis.

Fourteen Staphylococcus epidermidis strains were biotyped according to the scheme of Baird-Parker and tested for their sensitivities to S. epidermidis typing phages. Tetracycline-susceptible strains were tested for the capacity to be transduced to resistance. Five strains, all of biotype 1, were lysed by one or more phages. Five of eight biotype 1 strains were transduced to tetracycline resistance with rates of 10(-8) to 10(-5). Three strains of other biotypes were not transduced, nor was PS 73, an unusual coagulase-negative strain. The transducing phage phi367 was isolated from the lysogenic tetracycline-resistant donor strain. The phage morphologically resembles serological group B S. aureus phages. Restriction and modification were indicated from the efficiency of plating on phage-sensitive strains.

Bacteriolysis↗
PubMed1977

Lysis if enterobacteria by cefoxitin, cefuroxime, and cephalothin.

Cefoxitin, cefuroxime, and cephalothin were added to dense populations of beta-lactamase-producing enterobacteria, and the subsequent turbidity changes were monitored continuously. Viable counts and antibiotic assays were made at intervals after the addition of antibiotic, and the morphological appearances of the organisms were observed. Cephalothin caused lysis of most of the organisms tested, but even at high concentrations, after a few hours the antibiotic was destroyed and the organisms recommenced logarithmic growth. Cefoxitin produced lysis of all the strains of Escherichia coli and Klebsiella species tested, with supression of regrowth. With cephalothin and cefoxitin the viable counts after the addition of antibiotic correlated with the turbidity measurements. Cefuroxime infrequently caused lysis that suppressed multiplication, and the organisms became long and filamentous while the turbidity readings increased; the viable counts did not correlate with the turbidity measurements. Cefuroxime and cefoxitin were not destroyed by the beta-lactamases of any of the strains of enterobacteria that were studied.

Bacteriolysis↗
PubMed1977

Bacteriolytic action of fluoride ions.

Bacillus subtilis, Neisseria subflava, and LYT coccus were found to undergo massive lysis after growth in media containing 0.01 to 10 mM NaF. When cells of these organisms were transferred from late-exponential-phase cultures to 0.02 M sodium phosphate buffer plus 0.1 M KCl, they underwent spontaneous autolysis. Cells grown in media with fluoride were more liable to autolysis, and walls isolated from them also showed enhanced autolytic sensitivity, even though added fluoride did not directly stimulate autolysins. Sporadic or partial lysis occurred in populations of Streptococcus sanguis and Streptococcus mutans BHT or LM-7 after growth in fluoridated media. Most bacteria that were tested did not undergo fluoride-induced lysis. However, cells of all test bacteria were found to have reduced amounts of peptidoglycan per unit of cell weight when grown in the presence of fluoride. Incorporation of labeled lysine or glucosamine into peptidoglycan (Park-Hancock residue) was stimulated, instead of inhibited, by fluoride. However, fluoride also stimulated the loss of radioactivity from Park-Hancock residues of cells that had previously incorporated labeled lysine or glucosamine. Thus, fluoride appeared to enhance peptidoglycan turnover, and this turnover reduced the peptidoglycan contents of all bacteria tested, but induced lysis in only those bacteria that normally have highly active autolytic systems.

Bacteria↗
PubMed1977

Penicillins activate autolysins extracted from both Escherichia coli and Klebsiella pneumoniae envelopes.

Ampicillin at a 50-mug/ml concentration effects a doubling of the autolysis rate of cell envelopes isolated from Klebsiella pneumoniae Mir A12. This antibiotic increases also by two- to threefold the depolymerizing activity of both K. pneumoniae and Escherichia coli crude extracts on a labeled peptidoglycan-lipoprotein complex. Several other penicillins also activate autolysins.

Bacteriolysis↗
PubMed1979

Morphological changes of Escherichia coli induced by bicyclomycin.

Electron microscopic studies with Escherichia coli revealed that bicyclomycin inhibits septum formation and converts the cells to filamentous forms. The antibiotic induced high undulation and numerous blebs of the outer membrane. Sometimes cytoplasmic contents leaked into the lumen of the bleb through a disrupted region of the membrane. Breakage of the outer membrane or blebs led to cell lysis. Electron-dense masses of amorphous material and vesicles were found in the cytoplasm.

Anti-Bacterial Agents↗
PubMed1979

Oxacillin-induced lysis of Staphylococcus aureus.

Six clinical isolates of Staphylococcus aureus were compared for their relative susceptibilities to the killing effects of oxacillin. Three of the strains had minimum bactericidal concentrations which were >10 times the minimum bacteriostatic concentration for this antibiotic and were designated tolerant (Tol(+)). The other strains had minimum bactericidal concentrations which were comparable to the minimum bacteriostatic concentration (Tol(-)). Lysis curves of these strains revealed that the Tol(+) strains exhibited a diminished rate of lysis when inhibited by oxacillin. This reduced rate of lysis was reflected also in a reduced rate of viability loss when the cells were exposed to oxacillin. During log growth the uptake of [(14)C]glycerol by Tol(+) cells was 1.5-fold greater than that by Tol(-) cells. Glycerol-labeled cells of each phenotype secreted radioactivity when inhibited by oxacillin. However, the Tol(+) strains released over twice as much label as the Tol(-) strains. No difference in the proportion of lipid secreted by the two phenotypes was found. The behavior of 60 to 65% of the labeled material released by inhibited cells during both sodium dodecyl sulfate gel electrophoresis and Sepharose 6B chromatography corresponded to that of lipoteichoic acid. When the major component of secreted material was added to oxacillin-inhibited Tol(-) strains, an inhibition of the lytic response was observed. These results suggest that oxacillin tolerance in S. aureus could be related to the enhanced secretion of an autolysin inhibitor, such as lipoteichoic acid.

Bacteriolysis↗
PubMed1980

Comparative bactericidal effects of azlocillin and ticarcillin against Pseudomonas aeruginosa.

Azlocillin was relatively ineffective against actively growing cultures of Pseudomonas aeruginosa in tests of bacteriolytic and bactericidal activity in which ticarcillin demonstrated pronounced bactericidal effects over a wide range of concentrations. Microscopic observation showed that azlocillin generally induced the formation of filamentous cells of P. aeruginosa which lysed only slowly, but ticarcillin caused the production of spheroplasts and subsequent rapid lysis. During the course of the bactericidal tests, azlocillin was inactivated, presumably by the beta-lactamase produced by P. aeruginosa, and the filamentous cells resumed normal cell division and growth. In contrast, there was no loss of ticarcillin activity, and there was no evidence of resumption of growth of P. aeruginosa in the presence of ticarcillin. These results suggest that the different bactericidal effects demonstrated by azlocillin and ticarcillin against P. aeruginosa are related primarily to dose-related differences in inhibition of cell wall synthesis and secondarily to the instability of azlocillin to pseudomonal beta-lactamase.

Azlocillin↗
PubMed1980

Bactericidal activity of cerumen.

Freshly collected cerumen (dry form) suspended at a concentration of 3% in glycerol-sodium bicarbonate buffer showed bactericidal activity against some strains of bacteria tested. This suspension reduced the viability of Haemophilus influenzae, Escherichia coli K-12, and Serratia marcescens by more than 99%, whereas the viability of two Pseudomonas aeruginosa isolates, E. coli K-1, Streptococcus, and two Staphylococcus aureus isolates of human origin was reduced by 30 to 80%. The results support the hypothesis that cerumen functions to kill certain foreign organisms which enter the ear canal.

Adolescent↗
PubMed1981

Effects of penicillin on group A streptococci: loss of viability appears to precede stimulation of release of lipoteichoic acid.

The rate of killing of a group A streptococcal species by penicillin was compared with the release of lipoteichoic acid (LTA) and its deacylated derivative, dLTA. Although there was no stimulation of release from stationary-phase cells in the presence of penicillin, there was dramatic release of LTA and dLTA from exponential-phase cells after the addition of penicillin. Although decreases in viability were observed within 15 min after addition of penicillin, culture mass and LTA content did not appear to be affected until after 30 min. Stimulation of release of LTA and dLTA appeared to take place after 15 but before 30 min after addition of penicillin. These observations are interpreted to indicate that the stimulation of release of LTA and dLTA in response to penicillin is secondary to the killing event.

Bacteriolysis↗
PubMed1981

Cefmenoxime (SCE-1365), a novel broad-spectrum cephalosporin: in vitro and in vivo antibacterial activities.

The activity of cefmenoxime (SCE-1365), 7 beta-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid, was compared with that of other cephalosporins. Cefmenoxime exhibited high activity against a wide variety of gram-positive and gram-negative bacteria. The in vitro activity of cefmenoxime against Streptococcus pyogenes, Haemophilus influenzae, and Enterobacteriaceae, including indole-positive Proteus, Serratia marcescens, Enterobacter cloacae, and Citrobacter freundii, was 10 to 1,000 times greater than that of several other cephalosporins. Against Pseudomonas aeruginosa, cefmenoxime showed activity two to four times that of sulbenicillin and carbenicillin but less than that of cefsulodin. Variation in pH, addition of horse serum, and type of growth medium had definite effects on the activity of cefmenoxime, and the inoculum size affected the activity against bacterial species. In Escherichia coli cefmenoxime showed marked affinity for penicillin-binding protein 3 (PBP-3), followed by PBP-1 (1A and 1B). This affinity profile was well correlated with its filamentous cell-forming activity under extremely low drug concentrations and with its bactericidal activity against microorganisms. The high in vitro activity of cefmenoxime was reflected in the degree of protection observed in mice infected intraperitoneally with a wide variety of gram-positive and gram-negative bacteria. Furthermore, cefmenoxime showed good therapeutic activity against infection models in mice such as respiratory tract infection caused by Klebsiella pneumoniae and urinary tract infection caused by Proteus mirabilis.

Animals↗
PubMed1981

Activity of a new cephalosporin antibiotic, Ro 13-9904 against dense populations of selected enterobacteria.

Ro 13-9904 is a new cephalosporin antibiotic with a wide spectrum of activity similar to that of cefotaxime and some other newer beta-lactam compounds. In the present study, the response to Ro 13-9904 of 13 strains of enterobacteria, selected on the basis of differential patterns of susceptibility to beta-lactam agents, was investigated. The new cephalosporin displayed high intrinsic activity against most of the enterobacteria tested, but a group of Klebsiella and Hafnia alvei strains was identified against which Ro 13-9904 (and cefotaxime) exhibited reduced activity. Investigation of these strains revealed several different types of response to Ro 13-9904 and cefotaxime. Although such "difficult" strains represent a small minority of clinical isolates, it is likely that it is this group of strains against which the new generation of highly potent, broad-spectrum beta-lactam antibiotics will display significant differential activity.

Anti-Bacterial Agents↗
PubMed1981

Antibacterial properties of alafosfalin combined with cephalexin.

The phosphonopeptide alafosfalin (L-alanyl-L-1-aminoethylphosphonic acid) exhibited synergy in vitro and in animal studies against a range of bacterial genera when combined with cephalexin. Alafosfalin also showed synergy with mecillinam and, to a much lesser extent, with ampicillin. Synergy with cephalexin was more pronounced when the bacteria were relatively insensitive to the beta-lactam component. The action of this combination involved both an inhibitory and a bacteriolytic mechanism which was abolished by concurrent treatment with the aminopeptidase inhibitor, bestatin. Regrowth of subpopulation resistant to either component was markedly reduced by the combination. The potential of alafosfalin combined with cephalexin for use in therapy is discussed.

Alanine↗
PubMed1984

Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A.

The phosphonopeptide L- norvalyl -L-1- aminoethylphosphonic acid [ Nva -Ala(P)] has been studied in combination with 12 beta-lactam antibiotics for activity against Pseudomonas aeruginosa. Nocardicin A was found to give the most potent synergistic combination with Nva -Ala(P). This interaction was widely observed in clinical isolates of P. aeruginosa in vitro and in a mouse septicemia model. Synergy was also observed in vitro and in vivo in several other species, including Proteus mirabilis, indole-positive Proteus spp., and Serratia marcescens. The interaction between Nva -Ala(P) and nocardicin A involved a strongly bacteriolytic mechanism. In addition, the individual components were complementary to one another in their action against organisms not showing synergy. These properties resulted in a broad spectrum of activity of the combination Nva -Ala(P) plus nocardicin A when used to treat experimental gram-negative bacterial infections.

Alanine↗
PubMed1984

Protection by D-amino acids against growth inhibition and lysis caused by beta-lactam antibiotics.

D-Isomers of several amino acids completely protected growing cultures of Escherichia coli against all antibacterial effects of beta-lactam antibiotics up to approximately two to three times the MICs of the antibiotics. L-Isomers of amino acids were ineffective. Protection depended on the concentration and time of addition of the D-amino acids. This appears to be the first demonstration of natural products capable of reversing the antibacterial effects of beta-lactam antibiotics.

Amino Acids↗
PubMed1984

Teicoplanin, a new antibiotic from Actinoplanes teichomyceticus nov. sp.

Teicoplanin, a new glycopeptide antibiotic belonging to the same family as vancomycin, inhibits cell wall synthesis in Bacillus subtilis; the inhibition is accompanied by an intracellular accumulation of UDP-N-acetyl-muramyl-pentapeptide. A cell-free system from Bacillus stearothermophilus, capable of synthesizing peptidoglycan, is 50% inhibited by teicoplanin at 40 micrograms/ml and 100% inhibited at 100 micrograms/ml; suppression of peptidoglycan synthesis is accompanied by parallel accumulation of the lipid intermediate. Teicoplanin binds to cell walls and forms a complex with N,N'-diacetyl-L-lysyl-D-alanyl-D-alanine. The association constant of this complex is 2.56 X 10(6) liters mol-1, calculated by spectrophotometric titration. The mechanism of action of teicoplanin is discussed in comparison with those of other inhibitors of cell wall biosynthesis, namely, vancomycin, ristocetin, and gardimycin.

Acetylglucosamine↗
PubMed1985

Antagonistic effect of penicillin-amikacin combinations against enterococci.

Amikacin has been shown to antagonize the bactericidal effect of penicillin against strains of Streptococcus faecalis which produce aminoglycoside 3'-phosphotransferase. The mechanism by which this phenomenon occurs was studied with an enzyme-producing strain (8436) and an enzyme-negative strain (8436c) derived by curing the former with novobiocin. Combinations of amikacin with beta-lactam antibiotics were antagonistic against strain 8436 but synergistic against strain 8436c. Against strain 8436 penicillin-amikacin combinations resulted in levels of killing comparable to those seen with high concentrations of penicillin (500 micrograms/ml), which were less bactericidal than lower concentrations of penicillin. No antagonism was observed between amikacin and non-beta-lactam cell wall-active drugs or between penicillin and kanamycin or neomycin, both of which are substrates for the enzyme. At concentrations near the MIC, amikacin was bactericidal against strain 8436c but bacteriostatic against strain 8436 (MIC, 250 micrograms/ml; MBC, 2,000 micrograms/ml). Neither penicillin nor phosphorylated amikacin affected the inhibition of ribosomal protein synthesis by amikacin in a cell-free system. Although antagonism of killing by amikacin in enzyme-positive strains was specific for combinations which included beta-lactam antibiotics, amikacin did not influence the binding of [3H]penicillin to penicillin-binding proteins in isolated bacterial cell membranes or in intact cells and did not detectably affect the autolytic system of cells exposed to penicillin. Antagonism of beta-lactam activity by a bacteriostatic effect of amikacin against the enzyme-producing strain is the most likely explanation for this phenomenon.

Amikacin↗
PubMed1985

Correlation between growth curve and killing curve of Escherichia coli after a brief exposure to suprainhibitory concentrations of ampicillin and piperacillin.

Escherichia coli strains that were susceptible to multiple antibiotics were exposed to suprainhibitory concentrations of ampicillin and piperacillin. As with the majority of beta-lactam antibiotics, the growth curves showed an increase in optical density (OD) before lysis during the first hours. This increase in OD depended on the concentration of ampicillin and was independent of the concentration of piperacillin. A good correlation was found between the prelytic increase in OD and the killing curve. During the prelytic increase in OD, the number of CFU per milliliter remained constant. The decrease in the number of CFU per milliliter depended on the concentration of ampicillin and was independent of the concentration of piperacillin. pH variations gave rise to similar effects on growth curves and killing curves.

Ampicillin↗